Regulated expression of the renin-angiotensin-system in human granulosa lutein cells: angiotensin II increases VEGF expression but its synthesis is reduced by hCG.

Introduction: The Renin-Angiotensin-System (RAS) has been suspected not only to control vascular tone but also to regulate angiogenesis. Angiotensin II has been shown to influence angiogenic factors such as vascular endothelial growth factor (VEGF). The Corpus luteum undergoes intense VEGF-dependent angiogenesis, regulated by luteinising hormone (LH) and human chorionic gonadotrophin (hCG). We therefore hypothesised, that locally produced Angiotensin II could act as a physiological co-regulator with hCG in luteal VEGF expression.

Materials And Methods: We investigated the expression of RAS components and their regulation by hCG in human granulosa lutein cells using RT-PCR, immunocytochemistry and Western blotting. In addition, we studied the effect of Angiotensin II on basal and hCG-stimulated VEGF expression using TaqMan-analysis, ELISA, and Western blot analysis.

Results: Human granulosa lutein cells express angiotensinogen and angiotensin converting enzyme (ACE) and synthesise Angiotensin. In addition, they express both Angiotensin receptors. Angiotensin II stimulated VEGF mRNA (p < 0.05) and protein expression (p < 0.05). However, hCG decreased angiotensinogen (p < 0.05) and Angiotensin II (p < 0.05). Both, the addition of Angiotensin II and its inhibition using Candesartan did not change the magnitude of hCG-increased VEGF expression.

Conclusion: These findings suggest a role for locally synthesised Angiotensin II in the regulation of luteal VEGF expression. However, Angiotensin II does not appear to have a major contribution in the presence of hCG when the RAS pathway is down-regulated.